Dupuytren Contracture

▎药明康德内容团队编辑掌纤维瘤病（Dupuytren挛缩）是一种常见的遗传性纤维化疾病，通常发生在年龄大于45岁的男性身上。它的典型症状包括在手掌内形成结节，最终导致手指向内挛缩（爪形手）。这种疾病不仅会影响患者手部的活动度和功能，还会使人衰弱，并经常产生疼痛。或许很多人没有听说过这种疾病，但它的发病率为大众所耳熟能详的类风湿关节炎的3倍，影响了全球8.2%的人口，是最常见的致残性手部疾病之一。尽管掌纤维瘤病不会致命，但患有此类疾病的患者常常饱受这种疾病带来的痛苦。除了注射胶原酶，掌纤维瘤病患者没有更多的药物治疗可供选择，只能一遍又一遍地进行手术或放疗以阻止疾病的进展，但这些方法的效果通常只能暂时阻止疾病的进展。不仅如此，约85%的患者术后会复发，还有39%的患者会产生手术并发症。一部分患者如果不想再忍受多次手术的痛苦，甚至会选择截肢。对于该疾病患者来说，他们迫切需要新的药物疗法来改善他们的治疗现状。▲Ventoux Biosciences的创始人兼首席执行官Kurt Harrington先生（图片来源：Ventoux Biosciences公司官网）库尔特·哈林顿（Kurt Harrington）是生物技术行业的资深工作者，曾在多家生物医药公司担任过领导职务，同时也是一名掌纤维瘤病患者。自哈林顿三十多岁首次发病后，他至今已被此病困扰大约15年。在这期间，他已经接受了多轮手术和放疗治疗来控制疾病的进展。哈林顿的病遗传自他的父亲，他父亲在30多年的患病生涯中也已接受过八次手术。除了自己和父亲的病，最令哈林顿感到不安的是，他的两个儿子虽然年龄尚小还未发病，但也很有可能会遗传。为此，哈林顿决定自己筹款成立一家公司，为自己的孩子，也为全球数千万掌纤维瘤病患者找到新的有效的治疗之法。好消息是，今年3月12日，哈林顿创立的Ventoux Biosciences公司宣布，其主要候选疗法在临床前实验中取得了积极的结果，并已启动一轮融资，旨在将这种候选药物从临床前研究阶段推进到人体研究阶段。Ventoux Biosciences表示，其候选疗法VEN-201是一种已在全球90多个国家/地区使用了超过20年的疗法，其安全性已得到验证，但该分子此前并未获批用于治疗Dupuytren挛缩。Ventoux Biosciences通过针对性的科学评估、专家意见和人工智能数据发现了这种已获批的小分子具有治疗Dupuytren挛缩的潜力。该分子的具体信息尚未披露。在与掌纤维瘤病表型相似的硬皮病小鼠模型的实验中，与未经治疗的小鼠相比，每天将VEN-201注射到小鼠的纤维化组织中，可以减少其厚度和胶原蛋白的密度，并重塑整体组织。该结果表明，VEN-201具有一定的抗纤维化活性，需要在临床试验中进一步进行验证。对于这款正在尝试老药新用的疗法，哈林顿表示，尽管它无法治愈掌纤维瘤病，他还是希望它能够阻止这种疾病进一步恶化，让那些患者避免采取最极端的措施。他说：“如果我们能够及早为患者提供一些干预方法来帮助他们减缓疾病的进展，那就太好了。”大家都在看▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料：[1] A founder's quest for drug to treat his own hand condition kicks off with positive mouse data. Retrieved March 13, 2024, from https://www.fiercebiotech.com/research/founders-quest-drug-treat-his-own-hand-condition-kicks-positive-mouse-data[2] Dupuytren挛缩-默沙东诊疗手册（大众版）. Retrieved March 13, 2024, from https://www.msdmanuals.cn/home/bone-joint-and-muscle-disorders/hand-disorders/dupuytren-contracture[3] Ventoux Biosciences Launches To Transform Disease Management For Fibrotic Disease. Retrieved March 13, 2024, from https://www.ventouxbio.com/ventoux-biosciences-launches-to-advance-treatment-options-for-dupuytrens-disease/免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

VEN-201 wouldn't cure Dupuytren's contracture but could be used to keep it from reaching a point where more drastic measures are necessary.  The surgeons who treat it call it “the most common crippling hand disease you’ve never heard of”: Dupuytren's contracture, an incurable, sometimes painful disorder where cords of fibrotic tissue build up in the hand, causing the fingers to bend toward the palm.  “It’s so prevalent, but it hides in plain sight,” Kurt Harrington, a biotech industry veteran and founder of San Diego-based Ventoux Biosciences, told Fierce Biotech Research in an interview. About 5% of people in the U.S. have the disease, most of them over the age of 50. Harrington himself developed it much younger: Now in his 50s, his first symptoms showed up in his 30s. He’s since had multiple rounds of surgery and radiation to keep the condition at bay.  Those treatments and a drug called Xiaflex, marketed by Endo International, are the only therapies available to patients. Now, Ventoux is positioning itself to add another option. On March 12, the company announced that its lead candidate, a commercially available drug that the biotech has repurposed and renamed VEN-201, successfully reduces skin fibrosis in mice. Ventoux also revealed that it has launched a fundraising round to take the drug—the identity of which the biotech will not yet reveal—from preclinical research to a first-in-human study.  “It sounds corny, but I formed this company to literally try and make a difference,” Harrington said. He’s not the only one in his family who stands to benefit: His father has the disease, too, and just underwent his eighth surgery.  The results announced by Ventoux came from experiments on mouse models of scleroderma, a skin condition mechanistically similar to Dupuytren’s that causes tight, hard nodules to form in the skin. Daily injections of VEN-201 into the animals’ fibrotic tissue cut down on its thickness and the density of the collagen within it, as well as tissue remodeling overall, relative to untreated mice.  VEN-201 is a small molecule that already has FDA approval for other conditions; it has been used in more than 90 countries for over 20 years, according to the company. Ventoux is in the process of patenting it for use in Dupuytren’s and hasn’t yet disclosed the name of the repurposed drug. (If all goes according to plan, it’ll do so later this year, Harrington said.) There are at least three or four potential targets that it could be affecting, and previous research shows that it has some antifibrotic activity in other disease models, Ventoux Chief Scientific Officer Ken Lipson, Ph.D., explained.  While the mouse model used in the study is far from a mirror image of Dupuytren’s, “it’s encouraging that we have been able to reproduce or confirm that the agent that we’re going to be using does show some antifibrotic activity,” he said.  Ventoux was completely self-funded until last November, when Harrington began fundraising among friends and family. To take their proof-of-concept drug from animals to humans, he’s hoping to raise between $1.2 million and upward of $1.5 million from investors. He believes that the prevalence of the condition not just in the U.S. but in European countries combined with a relatively unsaturated market make developing treatments for Dupuytren's a good bet.  “We routinely say that in the U.S. and Europe alone, there’s over 40 million patients,” he said. “The market is extremely big.”  Harrington’s resume includes stints at AstraZeneca, Biogen and leadership roles at smaller startups with exits. While working at Biogen as a senior marketing manager, he was part of the team that launched the rheumatoid arthritis drug Rituxan in partnership with Roche's Genentech. That experience gave him the insight to draw comparisons between the market for rheumatoid arthritis drugs and for those that could treat Dupuytren’s.  “When you think about rheumatoid arthritis and the number of treatments for RA, there’s three or four different classes of drugs and upwards of 16 medications. Many of them are disease-modifying drugs,” Harrington said. “There are zero disease-modifying drugs for Dupuytren’s and yet it has three and a half times the prevalence of RA.”  While Dupuytren’s isn’t life-threatening, the ramifications can be serious. Surgery, radiation and Xiaflex only stop symptoms for a while, meaning patients will inevitably have to have more treatment as it progresses. They sometimes resort to amputation to keep from going through the cycle over and over again.  “It’s one of the more common reasons for elective amputation,” Harrington said. “They just get so at the end of their rope that there’s nothing else, and their fingers are almost in the way.”  Harrington is clear that VEN-201 will not be a cure for Dupuytren's. However, unlike the other options, he hopes it can be used to keep the disease from reaching a point where more drastic measures are necessary.  “If we can have something available early on to help patients and slow the disease down, it’ll be wonderful,” he said. 

DUBLIN, Jan. 24, 2024 /PRNewswire/ -- Endo International plc (OTC: ENDPQ) announced today that the peer-reviewed Journal of Hand Surgery Global Open published Collagenase Clostridium Histolyticum for the Treatment of Dupuytren Disease: A Delphi-Based Consensus Study.1 Consensus-based study findings among expert hand surgeons indicate that XIAFLEX® (collagenase clostridium histolyticum) has a wide-ranging application for the appropriate treatment of Dupuytren's contracture in patients with varying degrees of disease severity and functional impairment. Results from the published research indicate a high level of consensus for using XIAFLEX for the treatment of one- or two-finger metacarpophalangeal (MP) joint contractures, most one- or two-finger proximal interphalangeal (PIP) joint contractures, and most combined MP and PIP joint contractures. "Healthcare providers and patients can choose among multiple surgical and nonsurgical treatment options for Dupuytren's disease, and without established guidelines, the process for sorting through those choices can be overwhelming," said Dr. Gary M. Pess, a hand and upper extremity surgeon and lead author of the study. "This study provides insight from experienced hand surgeons about using XIAFLEX to treat varying degrees of Dupuytren's contracture." Dupuytren's disease is a heterogenous fibroproliferative condition of the palmar fascia characterized by the development of fascial nodules and cords that may result in digital contracture affecting hand function.2,3 XIAFLEX is a nonsurgical treatment option for Dupuytren's contracture when a "cord" can be felt composed of two purified collagenases that work to break down collagen when injected into fibrous tissue.4 About the Report Researchers used a modified Delphi method employing three successive, blinded online survey rounds to capture the clinical expertise of panelists and determine if consensus could be reached regarding the use of XIAFLEX for the treatment of Dupuytren's contracture.1 In Round 1, 22 real-world case scenarios were used to determine the panelists' recommendations for using XIAFLEX to treat metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joint contractures involving a single finger or 2 fingers, with varying degrees of contracture and clinical severity. Each scenario presented a distinct contracture(s) with a series of statements to evaluate the impact of patient- or disease-related features (e.g., age, recurrence, risk of anesthesia, Dupuytren diathesis, poor-quality skin, and post-fasciectomy scarring) on the clinical decision to use XIAFLEX. Researchers captured responses using either yes/no responses or a 5-point Likert scale ("strongly agree," "agree," "deficient information," "disagree," and "strongly disagree"). Level of agreement for each statement was determined, with a consensus threshold of ≥66.7% for agreement ("strongly agree" and "agree") or disagreement ("strongly disagree" and "disagree"). Round 2 included statements that did not meet the ≥66.7% threshold for consensus in round 1 and scenarios that explored the "impact of patient decision" (e.g., patient declines open surgical procedure). Statements were rated as described for round 1. Round 3 reassessed the statements that did not reach consensus in round 2 and explored the clinical decision-making process using an open-ended response methodology. Of the 33 hand surgeons who were invited based on their expertise and experience with treatment for Dupuytren's contracture, 22 agreed to participate in the survey; 20 completed round 1 of the survey, and 19 completed rounds 2 and 3. Overall, 80% had practiced medicine for at least 15 years, and all had completed a fellowship in hand surgery. Ninety percent were board-certified hand surgeons. Consensus-based study findings among expert hand surgeons point to wide-ranging application of XIAFLEX for the treatment of Dupuytren's contracture for patients with varying degrees of disease severity and functional impairment. WHAT IS XIAFLEX®? XIAFLEX is a prescription medicine used to treat adults with Dupuytren's contracture when a "cord" can be felt. It is not known if XIAFLEX is safe and effective in children under the age of 18. IMPORTANT SAFETY INFORMATION FOR XIAFLEX Do not receive XIAFLEX if you have had an allergic reaction to collagenase clostridium histolyticum or any of the ingredients in XIAFLEX, or to any other collagenase product. See the end of the Medication Guide for a complete list of ingredients in XIAFLEX. XIAFLEX can cause serious side effects, including: Tendon rupture or ligament damage. Receiving an injection of XIAFLEX may cause damage to a tendon or ligament in your hand and cause it to break or weaken. This could require surgery to fix the damaged tendon or ligament. Call your healthcare provider right away if you have trouble bending your injected finger (towards the wrist) after the swelling goes down or you have problems using your treated hand after your follow-up visit Nerve injury or other serious injury of the hand. After finger procedures, some people developed tears in the skin (lacerations), and local skin and soft-tissue necrosis (death of skin cells). Some lacerations and necrosis required skin grafting, or other surgery including amputation. Call your healthcare provider right away if you get numbness, tingling, increased pain, or tears in the skin (laceration) in your treated finger or hand after your injection or after your follow-up visit Hypersensitivity reactions, including anaphylaxis. Severe allergic reactions can happen in people who receive XIAFLEX because it contains foreign proteins. Call your healthcare provider right away if you have any of these symptoms of an allergic reaction after an injection of XIAFLEX: hives swollen face breathing trouble chest pain low blood pressure dizziness or fainting Fainting. Fainting (passing out) or near fainting can happen in people who receive XIAFLEX, especially following finger procedures If you have dizziness or feel faint after receiving XIAFLEX, lie down until the symptoms go away. Increased chance of bleeding. Bleeding or bruising at the injection site can happen in people who receive XIAFLEX. Talk to your healthcare provider if you have a problem with your blood clotting. XIAFLEX may not be right for you. Before receiving XIAFLEX, tell your healthcare provider if you have had an allergic reaction to a previous XIAFLEX injection, or have a bleeding problem or any other medical conditions. Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Using XIAFLEX with certain other medicines can cause serious side effects. Especially tell your healthcare provider if you take medicines to thin your blood (anticoagulants). If you are told to stop taking a blood thinner before your XIAFLEX injection, your healthcare provider should tell you when to restart the blood thinner. Ask your healthcare provider or pharmacist for a list of these medicines if you are unsure. The most common side effects with XIAFLEX for the treatment of Dupuytren's contracture include: swelling of the injection site or the hand bruising or bleeding at the injection site pain or tenderness of the injection site or the hand swelling of the lymph nodes (glands) in the elbow or armpit itching breaks in the skin redness or warmth of the skin pain in the armpit Tell your healthcare provider if you have any side effect that bothers you or does not go away. These are not all of the possible side effects with XIAFLEX. For more information, ask your healthcare provider or pharmacist. Click for full Prescribing Information, including Medication Guide. About Endo Endo (OTC: ENDPQ) is a specialty pharmaceutical company committed to helping everyone we serve live their best life through the delivery of quality, life-enhancing therapies. Our decades of proven success come from passionate team members around the globe collaborating to bring treatments forward. Together, we boldly transform insights into treatments benefiting those who need them, when they need them. Learn more at or connect with us on LinkedIn. Cautionary Note Regarding Forward-Looking Statements Certain information in this press release may be considered "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 and any applicable Canadian securities legislation including, but not limited to, the statements by Dr. Pess, any statements relating to product efficacy, potential treatments or indications, therapeutic outcomes or treatment responses, and any statements that refer to expected, estimated or anticipated future results or that do not relate solely to historical facts. Statements including words or phrases such as "believe," "expect," "anticipate," "intend," "estimate," "plan," "will," "may," "look forward," "intend," "guidance," "future," "potential" or similar expressions are forward-looking statements. All forward-looking statements in this communication reflect the Company's current views as of the date of this communication about its plans, intentions, expectations, strategies and prospects, which are based on the information currently available to it and on assumptions it has made. Actual results may differ materially and adversely from current expectations based on a number of factors, including, among other things, the outcome of the Company's contingency planning and restructuring activities; the timing, impact or results of any pending or future litigation, investigations, proceedings or claims, including opioid, tax and antitrust related matters; any actual or contingent liabilities; settlement discussions or negotiations; the Company's liquidity, financial performance, cash position and operations; the risks and uncertainties associated with chapter 11 proceedings; the time, terms and ability to complete a chapter 11 plan of reorganization or to pursue an alternative emergence transaction; the risk that the Company's chapter 11 cases may be converted to cases under chapter 7 of the Bankruptcy Code; the adequacy of the capital resources of the Company's businesses and the difficulty in forecasting the liquidity requirements of the operations of the Company's businesses; the unpredictability of the Company's financial results; the Company's ability to discharge claims in chapter 11 proceedings; negotiations with the holders of the Company's indebtedness and its trade creditors and other significant creditors; the risks and uncertainties with performing under the terms of the restructuring support agreement and any other arrangement with lenders or creditors while in chapter 11 proceedings; the performance, including the approval, introduction, and consumer and physician acceptance of new products and the continuing acceptance of currently marketed products; and the Company's ability to obtain and successfully manufacture, maintain and distribute a sufficient supply of products to meet market demand in a timely manner. The Company expressly disclaims any intent or obligation to update these forward-looking statements, except as required to do so by law. Additional information concerning risk factors, including those referenced above, can be found in press releases issued by the Company, as well as the Company's public periodic filings with the U.S. Securities and Exchange Commission and with securities regulators in Canada, including the discussion under the heading "Risk Factors" in the Company's most recent Annual Report on Form 10-K and any subsequent Quarterly Reports on Form 10-Q or other filings with the U.S. Securities and Exchange Commission. References Pess G, et al. J Hand Surg Online. 2023; 1-8. Warwick D, et al. Int. J Clin Rheumatol. 2012;7(3):309-323. Warwick D. J Hand Surg Eur Vol. 2017;42(7):665-672. XIAFLEX® (collagenase clostridium histolyticum) for injection, for intralesional use [package insert]. Malvern, PA: Endo Pharmaceuticals Inc. SOURCE Endo International plc